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NRF2 and Primary Cilia: An Emerging Partnership

Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), UAM-CSIC, 28029 Madrid, Spain
Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain
Instituto de Investigación del Hospital Universitario de La Paz (IdiPAZ), 28047 Madrid, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28013 Madrid, Spain
Author to whom correspondence should be addressed.
Current address: Centro Nacional de Investigaciones Oncológicas (CNIO), CSIC, 28029 Madrid, Spain.
Antioxidants 2020, 9(6), 475;
Received: 30 April 2020 / Revised: 30 May 2020 / Accepted: 31 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue Keap1/Nrf2 Signaling Pathway)
When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease. View Full-Text
Keywords: NRF2; primary cilia; hedgehog signaling; ciliogenesis; ciliopathy; cancer; autophagy; mTOR; non-small cell lung cancer (NSCLC) NRF2; primary cilia; hedgehog signaling; ciliogenesis; ciliopathy; cancer; autophagy; mTOR; non-small cell lung cancer (NSCLC)
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Martin-Hurtado, A.; Lastres-Becker, I.; Cuadrado, A.; Garcia-Gonzalo, F.R. NRF2 and Primary Cilia: An Emerging Partnership. Antioxidants 2020, 9, 475.

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